37 results about "Mast Cell Diseases" patented technology

The invention provides methods of treating a disease selected from systemic sclerosis, rheumatoid arthritis, mastocytosis, and chronic eosinophilic leukemia comprising administering biaryl meta-pyrimidine compounds having the general structure (A) to a subject in need thereof. The pyrimidine compounds of the invention are capable of inhibiting kinases, such as members of the JAK kinase family, and various other specific receptor and non-receptor kinases.

The invention provides a method for preventing and treating the harmful biological effects of biochemicals secreted from activated mast cells in the organism of warm blooded animals and more especially human beings, said effects being associated with allergy (including but not limited to allergic conjunctivitis, allergic rhinitis, allergic otitis, asthma, allergic uticaria, food allergy and atopic dermatitis), hyperproliferative diseases such as leukemia and systemic mastocytosis, interstitial cystitis, inflammatory bowel disease, irritable bowel syndrome, osteoporosis and scleroderma. The method consists in administering to said animals and especially to human beings an effective amount of a proteoglycan such as chondroitin sulfate with mast cell secretion inhibitory activity, alone or in combination with one or more synergistic adjuvants such those belonging to the class of flavonoids or compounds with histamine-1 receptor antagonist activity.

This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a methods of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a method of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

Compositions for protection against SVFS induced by niacin, a carcinoid, mesenteric traction, serotonin, post-menopause, alcohol, monosodium glutamate, mastocytosis, atopic dermatitis, food-allergy or food intolerance, and mast cell activation syndrome, or against individual symptoms of SVFS, superficial vasodilation, feeling of warmth, itching (pruritus) and hives, comprising a flavonoid compound of the structure 2-phenyl-4H-1-benzopyran or 2-phenyl-4-keto-1-benzopyran or glycosides thereof, or chalconoid compounds, with appropriate substitutions of their hydroxyl groups to render them water soluble or in combination with a pshospholipid or cyclodextrin to render them to have higher oral absorption, administered alone or together with an anti-superficial vasodilation dose of one or more of, olive kernel oil, a serotonin inhibitor, a prostaglandin inhibitor, willow bark extract. A composition for treating cardiovascular disease with niacin, but without eliciting the SVFS effects of niacin, has also been invented.

Non-allergic hypersensitivity reactions can be observed in a sample of cells from a subject in response to anaphylatoxins. Accordingly, methods are provided for detecting clinical conditions such as cellular hyper-reactivity, non-allergic hypersensitivity, asthma, inflammation, chronic or acute infection, bacterial infection, viral infection, parasite infection, adverse drug reaction, organ rejection, vasculitis, mastocytosis, eosinophilia, basophilia, leukemia, and / or C3a or C5a receptor defects in a subject. Also provided are kits for detecting such clinical conditions in a subject.

Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

The present invention relates to cell-based assays useful for screening for modulators, such as inhibitors, of activated mutant KIT tyrosine kinase receptors, which are associated with mast cell-related disorders, such as mastocytosis and various types of cancer. The invention further provides for the treatment of mast cell-related disorders with an inhibitor identified by the screening method.

Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein A, R1, X and Y are defined herein, are useful in the treatment of tumors and cancers such as mastocytosis / mast cell leukemia, gastrointestinal stromal tumors (GIST), germ cell tumors, small cell lung carcinoma (SCLC), sinonasal natural killer / T-cell lymphoma, testicular cancer (seminoma), thyroid carcinoma, malignant melanoma, ovarian carcinoma, adenoid cystic carcinoma, acute myelogenous leukemia (AML), breast carcinoma, pediatric T-cell acute lymphoblastic leukemia, neuroblastoma, mast cell leukemia, angiosarcoma, anaplastic large cell lymphoma, endometrial carcinoma, and prostate carcinoma.

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocytosis.

The invention relates to a purpose of a medicine which is prepared by triptolide and is used for curing tumor that is relevant to c-KIT tyrosine kinase. The invention verifies that a micromolecule natural product triptolide (TPL) can down-regulate the protein expression of D816V point mutation c-KIT for the first time, inhibit the phosphorylation thereof and induce the cell apoptosis of STI571 resistance c-KIT point mutation (D816). The invention discloses a novel micromolecule stayer of tyrosine kinase, more particularly overcomes the problem that the resistance property of the medicine STI 571 can be inhibited by the first-line tyrosine kinase that is used on the clinic at present. The TPL can be used for developing a novel specific medicine for curing tumors being relevant to c-KIT mutation, such as gastrointestinal stromal tumor, systemic mastocytosis and small cell lung cancer, etc.

A carboxylic acid compound represented by formula (I): (meanings of the symbols in the formula are as mentioned in the specification) and a pharmaceutical agent comprising the compound. <>Since the compound represented by formula (I) binds to a DP receptor and shows antagonistic activity for the DP receptor, it is useful for prevention and / or treatment of diseases such as allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like. Carboxylic acid compounds represented by the following general formula (I) (wherein each symbol is as defined in the description) and drugs containing these compounds: (I) Because of binding to DP receptor and antagonizing the same, the compounds represented by the general formula (I) are useful in preventing and / or treating allergic diseases (allergic nephritis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.), systemic mast cell disease, systemic mast cell activation failure, anaphylactic shock, respiratory tract contraction, urticaria, eczema, diseases associated with itch (atopic dermatitis, urticaria, etc.), diseases (cataract, retinal detachment, inflammation, infection, sleep disorder, etc.) secondarily caused by behaviors associating itch (scratching, beating.

Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein A, Q, Y, R5, m and J are defined herein, are useful in the treatment of tumors and cancers such as mastocytosis / mast cell leukemia, gastrointestinal stromal tumors (GIST), germ cell tumors, small cell lung carcinoma (SCLC), sinonasal natural killer / T-cell lymphoma, testicular cancer (seminoma), thyroid carcinoma, malignant melanoma, ovarian carcinoma, adenoid cystic carcinoma, acute myelogenous leukemia (AML), breast carcinoma, pediatric T-cell acute lymphoblastic leukemia, neuroblastoma, mast cell leukemia, angiosarcoma, anaplastic large cell lymphoma, endometrial carcinoma, and prostate carcinoma.

The disclosure is directed to methods of treating hematologic malignancies. More particularly, the disclosure is directed to methods of treating hematologic malignancies using Rho kinase (ROCK) inhibitors and myosin light chain-specific inhibitory RNA molecules. The disclosure is further directed to methods of identifying drug candidates for inhibiting ROCK in hematologic malignancies.

Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein A and J are defined herein, are useful in the treatment of tumors and cancers such as mastocytosis / mast cell leukemia, gastrointestinal stromal tumors (GIST), germ cell tumors, small cell lung carcinoma (SCLC), sinonasal natural killer / T-cell lymphoma, testicular cancer (seminoma), thyroid carcinoma, malignant melanoma, ovarian carcinoma, adenoid cystic carcinoma, acute myelogenous leukemia (AML), breast carcinoma, pediatric T-cell acute lymphoblastic leukemia, neuroblastoma, mast cell leukemia, angiosarcoma, anaplastic large cell lymphoma, endometrial carcinoma, and prostate carcinoma.

The treatment of mastocytosis, and in particular indolent forms of mastocytosis (including smoldering systemic, indolent systemic and cutaneous mastocytosis), including the administration of a tyrosine kinase inhibitor or a mast cell inhibitor, especially masitinib or a pharmaceutically acceptable salt or solvate thereof, in particular in an appropriate dosage regimen.

A carboxylic acid compound represented by formula (I): (meanings of the symbols in the formula are as mentioned in the specification) and a pharmaceutical agent comprising the compound. <>Since the compound represented by formula (I) binds to a DP receptor and shows antagonistic activity for the DP receptor, it is useful for prevention and / or treatment of diseases such as allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like. Carboxylic acid compounds represented by the following general formula (I) (wherein each symbol is as defined in the description) and drugs containing these compounds: (I) Because of binding to DP receptor and antagonizing the same, the compounds represented by the general formula (I) are useful in preventing and / or treating allergic diseases (allergic nephritis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.), systemic mast cell disease, systemic mast cell activation failure, anaphylactic shock, respiratory tract contraction, urticaria, eczema, diseases associated with itch (atopic dermatitis, urticaria, etc.), diseases (cataract, retinal detachment, inflammation, infection, sleep disorder, etc.) secondarily caused by behaviors associating itch (scratching, beating.

Novel disulfide derivatives useful for preventing or treating allergic diseases of the eye, nose, skin, ear, gastrointestinal tract, airways or lung and preventing or treating manifestations of systemic mastocytosis are disclosed. The disulfide derivatives act as mast cell stabilizers.

Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein A, Q, Y, R1, R2, and R5 are defined herein, are useful in the treatment of tumors and cancers such as mastocytosis / mast cell leukemia, gastrointestinal stromal tumors (GIST), germ cell tumors, small cell lung carcinoma (SCLC), sinonasal natural killer / T-cell lymphoma, testicular cancer (seminoma), thyroid carcinoma, malignant melanoma, ovarian carcinoma, adenoid cystic carcinoma, acute myelogenous leukemia (AML), breast carcinoma, pediatric T-cell acute lymphoblastic leukemia, neuroblastoma, mast cell leukemia, angiosarcoma, anaplastic large cell lymphoma, endometrial carcinoma, and prostate carcinoma.

The treatment of mastocytosis, and in particular indolent forms of mastocytosis (including smoldering systemic, indolent systemic and cutaneous mastocytosis), including the administration of a tyrosine kinase inhibitor or a mast cell inhibitor, especially masitinib or a pharmaceutically acceptable salt or solvate thereof, in particular in an appropriate dosage regimen.

The treatment of mastocytosis, and in particular indolent forms of mastocytosis (including smoldering systemic, indolent systemic and cutaneous mastocytosis), including administration of a tyrosine kinase inhibitor or a mast cell inhibitor, especially masitinib or a pharmaceutically acceptable salt or solvate thereof, in particular in an appropriate dosage regimen.

Use of the N-phenyl-2-pyrimidine-amine derivatives of formula I,in which the symbols and substituents have the meaning as given herein in free form or in pharmaceutically acceptable salt form in the manufacture of a pharmaceutical composition for the treatment of anergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden infant death syndrome, bronchopulmonary aspergillosis, multiple sclerosis or mastocytosis;

The present invention relates to use of mast cell carboxypeptidase as a marker for anaphylaxis or mastocytosis in serum, plasma or saliva samples. Detection of elevated mast cell caroboxypeptidase in for example serum samples is proposed for reducing false negatives in relation to diagnosis of anaphylaxis and various categories of mastocytosis by picking up serum tryptase-negative cases.